Immunoglobulin E (IgE)-mediated immune reactivity may be targeted against latent herpes-family viruses located within the inner ear. Our preliminary studies, measuring herpes virus-specific IgE in the sera of Meniere's patients, suggest that most patients with Meniere's disease possess such reactivity. Most control subjects do not. The recurrent and reversible Meniere's symptoms: episodic vertigo, fluctuating hearing loss, tinnitus, and fullness, could all be caused by a latent IgE-mediated inflammatory response. If such were the case, a possible sequence of events could include: (1) repetitive infection of the host with one or more of the herpes viruses leading to formation of virus-specific IgE: (2) a parallel development of viral latency within the neuronal cells of the vestibular ganglion: (3) episodic reactivation of the latent virus(es) resulting in extraneuronal antigen expression; (4) complexing of the expressed viral antigens with in-situ specific IgE resulting in local mast cell degranulation and release of chemotactic agents and vasoactive substances; and (5) the consequential development of vascular dilation and increased permeability resulting in formation of endolymphatic hydrops. The specific aims of this research proposal are: 1) To examine the serum of patients with Meniere's disease for the presence of IgE that has specific reactivity to proteins of viruses that are known to be associated with latent viral infections, specifically herpes simplex type 1 and 2, Epstein-Barr virus, cytomegalovirus and/or varicella-zoster virus; and to determine whether patients with Meniere's disease are significantly different than the general population in the presence of IgE that is specific to those viruses. 2) To identify and define the principal proteins in these viruses to which IgE reacts.